Risk Of Shorter Overall Survival Research Articles

Serum NOX4 as a Promising Prognostic Biomarker in Association with 90-Day Outcome of Severe Traumatic Brain Injury.

PurposeNicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is related to brain oxidative stress. We attempted to examine the association between serum NOX4 levels, severity and prognosis of severe traumatic brain injury (sTBI).MethodsWe measured serum NOX4 levels in 105 patients with sTBI. Trauma severity was assessed using Glasgow coma scale (GCS) and Rotterdam computed tomography (CT) classification. Study outcome data on death and worst outcome (Glasgow outcome scale score of 1–3) were collected at 90 days after trauma. Multivariate analyses were performed to determine independent factors for overall survival and worst outcome. Area under receiver operating characteristic curve (AUC) was estimated to assess prognostic predictive ability.ResultsSerum NOX4 levels were tightly correlated with GCS score (t=−5.843, P < 0.001) and Rotterdam CT score (t = 4.231, P < 0.001). During 90 days of follow-up, 50 participants (47.6%) experienced a worse outcome, 28 (26.7%) died and the mean overall survival time was 71.9 days (95% confidence interval (CI), 65.7–78.1 days). Serum NOX4 was independently associated with an increased risk of short overall survival (hazard ratio, 1.129; 95% CI, 1.039–1.228) or worse outcome (odds ratio, 1.053; 95% CI, 1.014–1.095). Serum NOX4 levels had a certain predictive value for the patient’s risk of mortality (AUC, 0.803; 95% CI, 0.714–0.874) or worse outcome (AUC, 0.780; 95% CI, 0.689–0.855). Moreover, its AUC was in the range of GCS score and Rotterdam CT score (both P > 0.05) and it significantly improved their AUCs (both P < 0.05).ConclusionSerum NOX4 levels in the acute phase of sTBI were associated with trauma severity, an increased risk of mortality and worse outcome, suggesting that serum NOX4 could be an important prognostic factor for sTBI.

Mutations in circulating cell‐free tumour DNA: Predictors of survival in hepatocellular carcinoma

AbstractBackgroundHepatocellular carcinoma (HCC) incidence is increasing worldwide and prognostic biomarkers are urgently needed to guide treatment and reduce mortality. Circulating cell‐free DNA of tumour origin (ctDNA) is a novel, minimally invasive means of determining genetic alterations in cancer. We determined the utility of ctDNA as a prognostic biomarker of survival in HCC.MethodsPlasma cell‐free DNA and matched germline DNA were isolated from patients with HCC (n = 51) and cirrhosis (n = 10). Targeted, multiplex PCR ultra‐deep sequencing was performed using a liver cancer‐specific primer panel for genes ALB, AMPH, APC, ARID1A, ARID2, ATM, AXIN1, BAZ2B, BRAF, CSMD3, CTNNB1, DSE, ERBB2, HNF1A, IGFR2, IGSF10, KEAP1, MET, TP53, UBR3, USP25, ZIC3 and ZNF226. Associations between mutations in ctDNA and overall survival were analysed using Cox proportional hazards modelling.Results114 putative mutations (70 unique) in were detected in plasma ctDNA in 35 of 51 patients with HCC (69%). On univariable analysis, CSMD3 gene mutations were associated with shorter overall survival (Logrank HR 3.18, 95% CI 1.14‐8.86, P = .027). The median survival time was 15.5 months (IQR 7.77‐16.5 months) in patients with CSMD3 mutations compared with the median survival of 26.5 months (IQR 16.93‐46.07 months) in patients without CSMD3 mutations. Other factors associated with overall survival were advanced BCLC stage (HR 16.52, 95% CI 2.22‐122.94, P = .006) and Child‐Pugh Class (CPC HR 7.98, 95% CI 2.31‐27.61, P = .001). Cox proportional hazards modelling showed mutations in CSMD3 remained a significant independent risk for shorter overall survival in HCC when adjusted for age, BCLC stage and Child‐Pugh class (HR 4.91, 95% CI 1.60‐15.02, P = .005).ConclusionDetection of CSMD3 mutations in plasma ctDNA is associated with reduced overall survival in HCC patients, adjusted for potential confounding factors.

Polymorphism of TNFRSF1 A may act as a predictor of severe radiation-induced oral mucositis and a prognosis factor in patients with head and neck cancer

The aim of this study was to evaluate the relationship between single nucleotide polymorphism (SNP) (-135 T>C) of TNFRSF1 A and the frequency of occurrence and severity of oral mucositis (OM) in patients with head and neck cancer (HNC) treated with radiotherapy (RT). This retrospective, cohort study included 60 patients with HNC treated with intensity-modulated radiation therapy (IMRT). TNFRSF1 A SNP analysis (-135 T>C) was performed by using molecular probes (TaqMan, ThermoFisher Scientific, Waltham, MA) in DNA isolated from peripheral blood (QIAamp DNA MiniKit; Qiagen, Germantown, MD). CC genotype was related to 4.5-fold higher risk of grade 2 OM after the second week of RT. Similarly, CC carriers had a significantly higher risk of severe (grade 3) OM after the fourth (6-fold) and fifth (7.5-fold) weeks of RT. The CC genotype of the TNFRSF1 A gene was significantly correlated with a higher risk of shorter overall survival (OS) (> 37 months follow-up period; hazard ratio [HR]=2.78). SNP (-135 T>C) of the TNFRSF1 A gene may act as a predictor of OM occurrence in patients with HNC treated with IMRT. The studied SNP may also serve as a prognostic factor in such cases.

Comparison of Overall Survival in High Risk Patients with Minimal Residual Disease after First-Line Treatment across Three Generations of Phase 3 Trials of the German CLL Study Group

Comparison of Overall Survival in High Risk Patients with Minimal Residual Disease after First-Line Treatment across Three Generations of Phase 3 Trials of the German CLL Study Group

Oncologic outcomes of patients with positive surgical margin after partial nephrectomy: a 25-year single institution experience

To evaluate oncologic outcomes and management of patients with microscopic positive surgical margin (PSM) after partial nephrectomy (PN) for renal cell carcinoma (RCC). We reviewed our database to identify patients who underwent PN between 1990 and 2015 for RCC and had PSM on final pathology. A 1:3 matching was performed to a negative surgical margin (NSM) cohort. Kaplan-Meier method and log-rank test were used to estimate survival and differences in outcomes, respectively. Cox proportional hazards models were conducted to estimate the Hazards ratio. A total of 2297 patients underwent PN at our institution, of which 1863 (81%) had RCC. Microscopic PSM was found in 34 (1.8%) RCC patients who were matched to 100 patients with NSM. Of these 34 patients, local recurrence (n=4), distant kidney recurrences (n=4), and metastases (n=5) developed during a median follow-up of 62months. Bilateral tumors/tumors in a solitary kidney (n=12/13, 92%), and multifocal tumors (n=7/13, 54%) were found in patients who developed recurrence/metastasis. PSM patients were at a higher risk of shorter overall survival (p=0.001), local recurrence-free survival (p=0.003), distant recurrence-free survival (p=0.032) and metastasis-free survival (p=0.018). There was statistically significant association between PSM and bilateral tumors, prior treated RCC at presentation and higher nephrometry score in multivariable model. There was a low rate of microscopic PSM in our large cohort of patients undergoing PN despite tumor complexity. Higher nephrometry score, bilateral tumors, and prior treated RCC independently predicted PSM which showed worse survival, recurrence and metastasis compared to patients with NSM.

Recommendations for the treatment of hepatitis C in 2017.

The goals of treatment is to eliminate HCV infection, stop or reverse histological changes, reduce the risk of hepatocellular carcinoma development and transmission of the infection to other individuals. According to the recommendation of the Polish Group of Experts for HCV in 2017 all patients with chronic HCV infection should receive treatment, but it is not recommended in patients at high risk of short overall survival. If access to therapy is restricted, priority should be given to patients whose HCV infection can lead to an unfavourable outcome of the disease within a short time frame, particular to individuals with liver cirrhosis, rapidly progressing liver fibrosis, extrahepatic manifestations of HCV infection, chronic kidney diseases, patients before and after organ transplantation. Current recommendations of Polish Group of Experts for HCV provide guidelines to select optimal medication, assessment of liver fibrosis, treatment efficacy, dealing with resistance to direct acting antivirals, monitoring for hepatocellular carcinoma, management of HBV/HCV coinfection and drug interactions. It constains also advice on treatment of special patients populations such as renal failure, liver transplant and hepatic decompensation, as well as retreatment of patients which failed interferon free therapy. Moreover specific recommendations of management patients infected with different genotypes with currently reimbursed regimens or those expected to become available shortly in Poland are also included.

Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis. From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled. According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients were in the advanced stage (BCLC-C) or in the intermediate stage (BCLC-B) but unfit or unresponsive to other therapeutic strategies. Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo, and analyzed according to the modified Response Evaluation Criteria in Solid Tumors. Sorafenib was administered at 800 mg/d, until radiological progression or occurrence of unacceptable adverse events (AEs). Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival. Forty-four patients were enrolled, 15 had intermediate HCC and 14 a Child-Pugh score of B7. AEs caused treatment interruption in 19 patients (43%), and median treatment duration was shorter in this subset (5 wk vs 19 wk, P < 0.001) and in the BCLC-C subgroup (13 wk vs 40 wk, P = 0.015). No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years. After 16 wk of treatment, 18 patients (41%) had stable disease or partial response. Patients with viral infection or BCLC-C were at higher risk of disease progression. ECOG, extrahepatic spread, macrovascular invasion, alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival. In patients with cirrhosis and HCC treated with sorafenib, AEs are a common cause of early treatment withdrawal. Vascular invasion and extrahepatic spread condition early response to treatment and survival. Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.

Circulating Levels of TNF Receptor II Are Prognostic for Patients with Peripheral T-cell Non–Hodgkin Lymphoma

Peripheral T-cell non-Hodgkin lymphomas (T-NHL) represent a small but heterogeneous and clinically aggressive subset of NHLs with a poor outcome. Cytokines or their receptors might be associated with the clinical outcome of these lymphomas. Therefore, we tested whether gene variations and serum levels of soluble TNF receptor (TNFR)I (sTNFRI), sTNFRII, interleukin (IL)-10, or sIL-4R are predictive for treatment response in T-NHLs. Peripheral blood DNA from 117 patients with T-NHL treated in prospective clinical trials was subjected to genotyping analysis. Whenever possible, pretreatment sera were obtained, and circulating levels of sTNFRI, sTNFRII, IL-10, and sIL-4R were determined with a specific capture enzyme-linked immunoassay. Patients characterized by TNFRI-609GG (rs4149570) showed a trend toward better event free survival [EFS; univariate: P = 0.041; multivariate: HR, 1.76; confidence interval (CI), 0.99-3.14 with P = 0.056]. A protective role of IL-10-1087A, -824T, and -597A reported in another study was not confirmed in our cohort. Patients with circulating levels of soluble TNFRII ≥2.16 ng/mL had a 2.07-fold increased relative risk for shorter overall survival (OS; univariate: P = 0.0034; multivariate: HR, 2.07; CI, 0.92-4.70 with P = 0.081) and a 2.49-fold higher risk for shorter EFS (univariate: P = 0.00068; multivariate: HR, 2.49; CI, 1.22-5.08 with P = 0.012). Elevations of circulating levels of sTNFRI, IL-10, and sIL-4R are frequent, but the clinical response in these patients is not significantly different. Our findings suggest a critical role for TNF-TNFR signaling for the clinical outcome of patients with peripheral T-NHLs.

Preoperative Survivin mRNA Detection in Peripheral Blood is an Independent Predictor of Outcome in Esophageal Carcinoma

Survivin (SVV) mRNA expression levels in peripheral blood of patients with gastrointestinal malignancies change significantly during the course of treatment. We wanted to scrutinize these findings in patients with esophageal carcinoma and furthermore evaluate whether the detection of mRNA and the change in detecting ability have an association with overall survival. Whole blood was drawn 1 day pre- and 10 days post-operatively from 62 patients with esophageal carcinoma. Tumor cells were enriched from whole blood by density-gradient centrifugation prior to extraction of total cellular RNA and subsequent direct quantitative reverse transcriptase-PCR assays. SVV was detectable in 48 out of 62 patients (77%). Stepwise multivariate Cox linear regression models demonstrated a significant and independent association of measured SVV with overall survival (6.6 exp[b]; 95% CI: 1.97-22.12; p = 0.002). Increased SVV levels after the operation were linked to shorter overall survival (p = 0.04). Preoperative SVV expression levels appear to be associated with overall survival in patients with esophageal cancers. Increasing levels could potentially indicate a higher risk for shorter overall survival and therefore demand adapted treatment modalities.